The overall objective of this program project is to study several major components of high dose conformal therapy in order to optimize our ability to plan and deliver this kind of therapy. Only after the technical and clinical issues involved in conformal therapy are understood and optimized will formal tests of the clinical efficacy be possible. The projects proposed here will optimize our ability to 1) plan and evaluate conformal plans, 2) create sophisticated dose distributions, 3) improve the geometrical precision with which we treat patients, and 4) determine the clinical dose constraints for tumor and normal tissue doses which will be used for these conformal treatments. The University of Michigan has a unique ability to perform this work, based on its six years of experience with clinical 3-D treatment planning and dose escalation using static conformal therapy, the availability of several computer-controlled conformal therapy machines, and four years of work on the methodology to be used for conformal treatment delivery. In Project 1, we will develop several methods for optimization of treatment plans for use with computer-controlled conformal therapy techniques, including interactive, volumetric, and computer-automated optimization techniques, and then perform a clinical treatment planning study to evaluate the usefulness of the techniques in the clinical treatment sites studied in Project 4. In Project 2, we will develop several techniques which should optimize our ability to create desirable dose distributions, through the use of conformal field shaping and beam intensity modulation, and followed by evaluation of the clinical constrains and usefulness of the various techniques. In Project 3, we will study the precision with which patient localization, and target volume verification can be achieved, and will develop methods to minimize the geometric margins which must be used. In Project 4, we use a series of clinical dose escalation trials in prostate, brain, liver, and lung cancer, and a normal tissue dose reduction study in the head and neck area, to attempt to obtain the tumor and normal tissue tolerance dose limits which will allow the optimization of the dose distributions which should be delivered for these various diseases. All four projects are supported by three cores: Core A, which supports administration and statistics for the program project; Core B, which provides clinical physics, treatment planning and dosimetry support; and Core C, which supports computer programming and digital imaging support required by the various projects.